United States Patent 4,847,265: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 4,847,265, issued to Sanofi-Synthelabo, is a pivotal patent in the pharmaceutical industry, particularly in the context of cardiovascular medications. This patent revolves around the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate, commonly known as clopidogrel, and its pharmaceutically acceptable salts.
Patent Overview
Invention Description
The patent describes the dextro-rotatory enantiomer of clopidogrel, its process of preparation, and pharmaceutical compositions containing it. Clopidogrel is an antiplatelet medication used to reduce the risk of heart disease and stroke by inhibiting platelet aggregation[4].
Chemical Structure and Enantiomers
The patent specifies the chemical formula of clopidogrel and distinguishes between its dextro-rotatory (I d) and levo-rotatory (I l) enantiomers. The dextro-rotatory enantiomer is the active form claimed in the patent, highlighting its unique biological properties compared to the levo-rotatory enantiomer[4].
Claims
Primary Claims
The patent includes several key claims:
- Claim 1: The dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate.
- Claim 3: The hydrogen sulfate (bisulfate) salt of the dextro-rotatory enantiomer, which is the form commonly used in pharmaceutical applications[1][4].
Dependent Claims
The patent also includes dependent claims that cover various aspects of the invention, such as different salts (hydrochloride, hydrobromide, taurocholate), processes for preparing these compounds, and pharmaceutical compositions containing them[4].
Patent Landscape
Related Patents and Applications
Several other patents and applications are related to this invention:
- Polymorphic Forms: Other patents and PCT applications describe different polymorphic forms of clopidogrel salts, such as Form II of the hydrogensulphate salt and various forms of the hydrobromide and hydrochloride salts[3].
- Tablet Formulations: Patents like EP1970054A2 focus on specific tablet formulations of clopidogrel, including processes to reduce sticking to the punch during tablet manufacturing[3].
Litigation and Legal Context
The patent was at the center of significant litigation, particularly in the case of Sanofi-Synthelabo v. Apotex Inc. Apotex sought to manufacture and sell generic clopidogrel bisulfate tablets before the patent's expiration by filing an Abbreviated New Drug Application (ANDA) with the FDA. Apotex certified that the patent was invalid, leading to a lengthy legal battle over patent validity and infringement[1][5].
Infringement and Validity Challenges
Infringement
Apotex acknowledged that their generic product infringed claim 3 of the '265 patent but challenged the patent's validity on several grounds, including anticipation by prior art, obviousness, and obviousness-type double patenting[1].
Validity
The challenges to the patent's validity included allegations of inequitable conduct by Sanofi before the U.S. Patent and Trademark Office, such as failing to name an inventor and making false statements about the compound's properties[1].
Market Impact and Exclusivity
Market Exclusivity
The '265 patent was exclusively licensed to the Bristol-Myers Squibb Sanofi Pharmaceuticals Holding Partnership and expired on November 17, 2011. Apotex, as the first ANDA filer to challenge the patent, secured 180 days of market exclusivity under the Hatch-Waxman Act[1].
Generic Competition
The expiration of the '265 patent and the subsequent entry of generic competitors significantly altered the market landscape for clopidogrel, making the drug more accessible and affordable for patients.
Jury Trials and Declaratory Judgments
In the context of patent litigation, the case highlighted issues related to jury trials and declaratory judgments. The Federal Circuit has addressed the right to a jury trial in similar cases, emphasizing the distinction between legal and equitable remedies and the applicability of the Seventh Amendment[2].
Conclusion and Key Takeaways
- Unique Biological Properties: The '265 patent highlights the unique biological properties of the dextro-rotatory enantiomer of clopidogrel.
- Patent Claims: The patent includes claims for the dextro-rotatory enantiomer, its salts, and pharmaceutical compositions.
- Litigation: The patent was central to significant litigation involving generic manufacturers and challenges to its validity.
- Market Impact: The patent's expiration led to increased generic competition and reduced drug costs.
- Legal Precedents: The case contributed to legal precedents regarding jury trials and declaratory judgments in patent litigation.
Key Takeaways
- The '265 patent is crucial for understanding the development and commercialization of clopidogrel.
- The patent's claims cover the active enantiomer and its salts, which are essential for pharmaceutical applications.
- Litigation surrounding the patent set important legal precedents in the pharmaceutical industry.
- The expiration of the patent led to significant market changes, including increased generic competition.
Frequently Asked Questions (FAQs)
What is the main compound described in the '265 patent?
The main compound is the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate, known as clopidogrel.
Why is the dextro-rotatory enantiomer important?
The dextro-rotatory enantiomer has unique biological properties that make it effective as an antiplatelet medication, unlike its levo-rotatory counterpart.
What was the outcome of the litigation between Sanofi and Apotex?
The litigation involved challenges to the patent's validity and infringement. While Apotex acknowledged infringement, the case focused on the patent's validity, with Apotex asserting that the patent was invalid or unenforceable.
What is the significance of the Hatch-Waxman Act in this context?
The Hatch-Waxman Act provided Apotex with 180 days of market exclusivity as the first ANDA filer to challenge the patent, and it governed the process for generic drug approval and patent challenges.
When did the '265 patent expire?
The '265 patent expired on November 17, 2011.
Cited Sources:
- Sanofi-Synthelabo, Inc. v. Apotex Inc. - Casetext
- Sanofi-Synthelabo v. Apotex Inc., No: 02 Civ. 2255 (RWS) - Casetext
- EP1970054A2 - Clopidogrel tablets - Google Patents
- US4847265A - Dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate and the pharmaceutical compositions containing it - Google Patents
- Sanofi-Synthelabo v. Apotex, 550 F.3d 1075 - Casetext
